Anthracimycin activity against contemporary methicillin-resistant Staphylococcus aureus.
Hensler. Mary E ME; Jang. Kyoung Hwa KH; Thienphrapa. Wdee W; Vuong. Lisa L; Tran. Dan N DN; Soubih. Evaristus E; Lin. Leo L; Haste. Nina M NM; Cunningham. Mark L ML; Kwan. Bryan P BP; Shaw. Karen Joy KJ; Fenical. William W; Nizet. Victor V
Key Findings
- Anthracimycin kills MRSA at very low concentrations (ā0.25āÆmg/L) and achieves >4ālog reduction in 3āÆhours.
- It works together with the natural human peptide LLā37 to enhance bacterial killing.
- Shows low toxicity to human cells and protects mice from MRSA infection in a single dose.
Practical Outcomes
- For now, anthracimycin is a promising research lead for future antibiotics, not a practical tool for personal health optimization. Biohackers should watch its development but canāt apply it directly.
Summary
Anthracimycin is a new marineāderived compound that can kill MRSA bacteria very quickly in lab tests and even saved mice from deadly infections, but it isnāt a supplement you can buy or use yourself yet.
Abstract
Anthracimycin is a recently discovered novel marine-derived compound with activity against Bacillus anthracis. We tested anthracimycin against an expanded panel of Staphylococcus aureus strains in vitro and in vivo. All strains of S. aureus tested, including methicillin-susceptible, methicillin-resistant (MRSA) and vancomycin-resistant strains of S. aureus, were susceptible to anthracimycin at MIC values of ⩽0.25 mg l(-1). Although its postantibiotic effects were minimal, anthracimycin exhibited potent and rapid bactericidal activity, with a >4-log kill of USA300 MRSA within 3 h at five times its MIC. At concentrations significantly below the MIC, anthracimycin slowed MRSA growth and potentiated the bactericidal activity of the human cathelicidin, LL-37. The bactericidal activity of anthracimycin was somewhat mitigated in the presence of 20% human serum, and the compound was minimally toxic to human cells, with an IC50 (inhibitory concentration 50)=70 mg l(-1) against human carcinoma cells. At concentrations near the MIC, anthracimycin inhibited S. aureus nucleic acid synthesis as determined by optimized macromolecular synthesis methodology, with inhibition of DNA and RNA synthesis occurring in the absence of DNA intercalation. Anthracimycin at a single dose of 1 or 10 mg kg(-1) was able to protect mice from MRSA-induced mortality in a murine peritonitis model of infection. Anthracimycin provides an interesting new scaffold for future development of a novel MRSA antibiotic.
Study Information
pubmed
2014
2014-04-16T00:00:00.000Z
10.1038/ja.2014.36
36
15